Therapeutic angiogenesis, the desirable growth of new blood vessels, holds promise for stopping and even reversing the degenerative processes associated with peripheral arterial disease. In the absence of safe and effective means for revascularizing ischemic limbs, patients suffer pain, ulcers, and amputation. Gene transfection with vascular phVEGF(165) DNA plasmid is an effective means of stimulating new blood vessel growth and obtaining peripheral limb vascular disease reversal. However, safer and more effective methods for in vivo gene transfection are needed. PharmaSonics has demonstrated: (a) Ultrasound treatment dramatically increases reporter gene expression in skeletal muscle injected with naked DNA plasmid. (b) In young rabbits, ultrasound mediated gene transfection yields comparable angiogenesis at 1/5 the DNA dosage needed without ultrasound. (c) In old rabbits the plasmid induced angiogenic response is about twice as great with UGeneRx treatment than without. And, (d) biosafety studies show that the associated ultsasound levels do not cause tissue trauma. In this Phase 2 application, PharmaSonics is requesting funding to develop a clinical UGeneRx delivery probe. This probe will be tested in animals to verify efficacy and safety in order to then commence human clinical trials. PROPOSED COMMERCIAL APPLICATIONS: The demand for a therapy that can safely revascularize the ischemic limbs of millions of patients is self evident.